Dengue virus (DENV) is a mosquito-borne flavivirus that is spreading at an unprecedented rate and has developed into a major health and economic burden in over 50 countries. Current DENV vaccines protecting against all four DENV serotypes must be delivered as a “tetravalent” formulation of four viruses or four recombinant proteins, each intended to confer protection against that serotype. The correct mix of serotypes in the tetravalent cocktail to achieve a balanced antibody response is not known, underscored by the recent failure of the most advanced tetravalent live attenuated chimeric virus to provide clinically meaningful protection in a large phase 2B trial in Thailand (Sabchareon et al., 2012). Viral interference is thought to contribute to failure as one or more virus serotypes out-compete the others.
The present invention overcomes previous shortcomings in the art by providing chimeric dengue viruses that induce neutralizing antibodies against more than one dengue virus serotype from a single source.